Dataset Information

Protein Phosphatase 1 regulates atypical chromosome segregation and cell polarity during mitotic and meiotic division in Plasmodium sexual stages

ABSTRACT: PP1 is a conserved eukaryotic serine/threonine phosphatase that regulates many aspects of mitosis and meiosis, often working in concert with other phosphatases, such as CDC14 and CDC25. The proliferative stages of the parasite life cycle include sexual development within the mosquito vector, with male gamete formation characterized by an atypical rapid mitosis, consisting of three rounds of DNA synthesis, successive spindle formation with clustered kinetochores, and a meiotic stage during zygote to ookinete development following fertilization. It is unclear how PP1 is involved in these unusual processes. Using real-time live-cell imaging, conditional gene knockdown, RNA-seq and proteomic approaches, we show that Plasmodium PP1 is involved in both chromosome segregation during mitotic exit, and potentially establishment of cell polarity during zygote development in the mosquito midgut, suggesting that chemical inhibitors of PP1 may be explored for blocking parasite transmission

INSTRUMENT(S): Orbitrap Fusion

ORGANISM(S): Plasmodium Berghei Anka

SUBMITTER: Andrew Bottrill

LAB HEAD: Dr. Rita Tewari

PROVIDER: PXD023571 | Pride | 2021-09-10

REPOSITORIES: Pride

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Publications

Protein phosphatase 1 regulates atypical mitotic and meiotic division in Plasmodium sexual stages.

Zeeshan Mohammad M Pandey Rajan R Subudhi Amit Kumar AK Ferguson David J P DJP Kaur Gursimran G Rashpa Ravish R Nugmanova Raushan R Brady Declan D Bottrill Andrew R AR Vaughan Sue S Brochet Mathieu M Bollen Mathieu M Pain Arnab A Holder Anthony A AA Guttery David S DS Tewari Rita R

Communications biology 20210618 1

PP1 is a conserved eukaryotic serine/threonine phosphatase that regulates many aspects of mitosis and meiosis, often working in concert with other phosphatases, such as CDC14 and CDC25. The proliferative stages of the malaria parasite life cycle include sexual development within the mosquito vector, with male gamete formation characterized by an atypical rapid mitosis, consisting of three rounds of DNA synthesis, successive spindle formation with clustered kinetochores, and a meiotic stage durin ...[more]

PMID: 34145386

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Project description:A deeper understanding of malaria parasite development inside the Anopheles mosquito may lead to the identification of processes that can be targeted by transmission-blocking interventions. Paraquat (1,1'-dimethyl-4,4'-bipyridylium dichloride) is a potent superoxide-inducing agent that impacts Plasmodium ookinete development, especially at higher concentrations. Compounds like Paraquat can potentially induce an oxidative imbalance in the mosquito midgut during ookinete maturation, essentially super-stressing the parasite leading to the arrested development of ookinetes, the only stage that can invade through a mosquito midgut cell to establish an oocyst infection in the mosquito. The mosquito midgut has evolved to handle the natural production of reactive oxygen and nitrogen species (ROS and RNS, respectively) as a result of feeding on blood. The addition of Paraquat to a bloodmeal is expected to induce a cognate response in the midgut to handle the excess ROS/RNS, and high concentrations of this compound can potentially overwhelm the midgut response leading to mosquito death. While several studies have explored the effect of Paraquat on malaria parasites, a fundamental understanding of the mosquito response to this compound remains unknown. Here, we quantified the mosquito midgut proteomic response to a Paraquat-laced sugar meal to understand the intrinsic midgut response (in the absence of a bloodmeal). We then carried out transcriptomic analysis of the mosquito midgut for several antioxidants of the Trx and GSH pathways to compare concordance or discordance between protein and its transcripts during different oxidative stress conditions. Finally, we determined whether the same Trx and GSH pathways are upregulated following infection with either P. falciparum or P. berghei at 24 hrs post-blood feeding, coinciding with the time point for maximal ookinete traversal of the midgut. We discuss the potential selective action of Paraquat on the parasite and the intrinsic tolerance of the mosquito midgut to Paraquat-mediated oxidative stress.

Dataset Information

Protein Phosphatase 1 regulates atypical chromosome segregation and cell polarity during mitotic and meiotic division in Plasmodium sexual stages

Publications

Protein phosphatase 1 regulates atypical mitotic and meiotic division in Plasmodium sexual stages.

Similar Datasets

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